Ventricular Assist Device Therapy Research Articles

In vivo evaluation of two adaptive Starling-like control algorithms for left ventricular assist devices.

The implantation of a left ventricular assist device (LVAD) is often the only therapy in terminal heart failure (HF). However, despite technical advancements, the physical fitness of the patients is still limited. One strategy to improve the benefits of ventricular assist device therapy might be the implementation of load adaptive control strategies. Two control strategies and a constant speed controller (CS) were implemented in an acute animal model where four healthy pigs received LVAD implantations. In the first strategy (preload recruitable stroke work [SW] controller, PRS), the desired pump work was computed in relation to the end-diastolic volume. In the second strategy, the controller was programmed to keep a fixed ratio of the mean hydraulic power of the assist device to the mean hydraulic power of the left ventricle (power relation controller, PR). Preload reduction, afterload increase experiments and short-term coronary artery occlusions were conducted to test the behavior of the control strategies under variable conditions. Within the experiments, the PR controller demonstrated the best preload sensitivity. The PRS controller had the best response to an increased afterload and to a reduced ventricular contractility in terms of effectively preventing ventricular overloading and increasing VAD support. No significant differences in systemic flow were observed.

Mechanical circulatory support as a bridge to candidacy in adults with transposition of the great arteries and a systemic right ventricle.

Clinical experience with continuous flow ventricular assist devices (VADs) in patients with transposition of the great arteries (TGA) including dextro-TGA and congenitally corrected TGA is rare, and indications as well as potential benefits or specific hurdles remain unclear. Therefore, our goal was to report on our experience regarding VAD therapy in adult patients with TGA as a bridge to candidacy. We performed a single-centre retrospective study of all adult patients with TGA with systemic right ventricular failure who had continuous flow VAD implants between 2010 and 2018. Study end points were all causes of death, major cardiac and cerebrovascular adverse events or pump thrombosis. Follow-up continued until the time of the heart transplant. A total of 6 patients (4 men) had a continuous flow VAD implanted in the context of a failing systemic right ventricle (dextro-TGA after the Mustard procedure: n = 3; congenitally corrected TGA: n = 3). Demographics: mean age 32 ± 5.7 years; median Interagency Registry for Mechanically Assisted Circulatory Support: level II (range 1-4), mean pulmonary artery 48 ± 13 mmHg, mean pulmonary vascular resistance 5.6 ± 3.5 Wood units. Postoperative data: intensive care unit stay: 16 ± 9.7 days; in-hospital survival: 100%; no early VAD-related complications occurred. Mean follow-up: 33 ± 18 months; persistent left-side paresis: n = 1; minor (non-disabling) stroke: n = 2. Post-VAD pulmonary artery: 19 ± 3.4 mmHg; P < 0.005; post-VAD pulmonary resistance: 2.2 ± 0.55 Wood units; P = 0.066. Four patients had heart transplants after a mean waiting time of 30 months after the VAD was implanted; 2 patients are still on the waiting list (waiting time: 52 and 24 months). Continuous flow VAD therapy is a feasible therapeutic option in adult patients with TGA and a failing systemic right ventricle as a bridge to candidacy and a bridge to a heart transplant.

Sex differences in continuous-flow ventricular assist device therapy for advanced heart failure.

The effect of patient sex in continuous-flow ventricular assist device (c-VAD) therapy has not been well described. We investigated sex-specific differences in clinical outcomes related to c-VAD therapy for Japanese patients. We retrospectively analyzed 153 patients, including 41 (27%) female patients who underwent c-VAD implantation over the last 13years in our institution for a mean follow-up of 766 ± 446days. Clinical outcomes were compared between male and female patients RESULTS: There was no significant difference in mortality, cerebral vascular accidents, the severity of heart failure, or driveline infection in patients who underwent c-VAD implantation, regardless of sex. While male patients tended to have more bleeding at the time of surgery, female patients had significantly higher rates of non-surgical bleeding during subsequent c-VAD therapy, mainly from gynecological origins. Female patients treated with c-VAD had a significantly higher incidence of non-surgical bleeding events. Careful attention to gynecological complications and sex-specific care is required in female patients with c-VAD.

Corrections: Short- and long-term outcomes of continuous-flow left ventricular assist device therapy in 79 patients with end-stage heart failure.

Corrections: Short- and long-term outcomes of continuous-flow left ventricular assist device therapy in 79 patients with end-stage heart failure.

Survival After Heart Transplant Listing for Infants on Mechanical Circulatory Support

BackgroundInfants with heart failure remain at significant risk for wait list mortality, despite mechanical circulatory support (MCS). It is unclear if the outcomes are influenced by modality of support or underlying diagnosis. We sought to compare the outcomes of infants <10 kg, focusing on modality of support and underlying diagnosis.Methods and ResultsUsing the Pediatric Heart Transplant Society database, we evaluated survival following first MCS device in children <10 kg who were listed for heart transplant between 2010 and 2018. There were 2049 children <10 kg, with the predominant diagnosis being congenital heart disease (CHD) (59.8% [n=1226]) and 28.1% (n=577) requiring MCS. Extracorporeal membrane oxygenation (ECMO) was the most common form of MCS at listing, with ventricular assist device (VAD) more common after listing. There was no difference in the use of ECMO at or after listing for cardiomyopathy versus CHD (8.9% versus 7.2%; P=0.2; 5.4% versus 6.4%; P=0.4). However, there was a significant difference in the use of VAD both at listing (8% versus 2.4%; P<0.001) and after (22.8% versus 5.1%; P<0.001) between the 2 groups. When comparing these groups, patients with CHD were smaller and younger and had a higher proportion with previous cardiac surgery. Survival at 3 months demonstrated better survival for VAD therapy compared with ECMO (74.3% versus 48.6%; P<0.001). In patients <5 kg, survival did not differ between ECMO and VAD (P=0.01) for the CHD or the cardiomyopathy group (P=0.38), but patients with cardiomyopathy demonstrated better survival on both forms of support.ConclusionsSurvival for patients <10 kg on ECMO is inferior compared with VAD. Patients with cardiomyopathy <5 kg had better survival with both modes of MCS compared with those with CHD. These findings support the need for small, durable devices for neonates and infants, with particular focus in patients with CHD.

Poor Functional Status Prior to Bridge-to-transplant Left Ventricular Assist Device Therapy is not Associated with Reduced Survival in Heart Transplant Recipients: Analysis of the United Network for Organ Sharing (UNOS) Registry

Introduction Left ventricular assist devices (LVAD) are commonly used as a bridge-to-transplant (BTT) therapy for patients with advanced heart failure. Poor functional status (FS) is known to negatively affect post-transplant outcomes after heart transplant (HTX). In this study, we sought to evaluate the impact of poor FS prior to BTT-LVAD implantation on post-HTX outcomes. Methods Data from the UNOS database from 2008-2017 were obtained for HTX recipients that underwent continuous-flow LVAD implantation after being listed for HTX with complete Karnofsky Performance Status (KPS) score both at listing (Pre-LVAD) and time of HTX. Poor FS was defined by KPS ≤ 40 (require total assistance) and good FS was defined by KPS > 40 (require some or no assistance). Improvement of FS was defined as a change from pre-LVAD poor FS to good FS at HTX. Multivariate logistic regression adjusting for baseline/pre-HTX characteristics was performed to assess the association of pre-LVAD FS and post-HTX survival and predictors of FS improvement. Results We included 2,812 patients (mean age 52 years, 80% male, 41% on inotrope) listed for HTX before LVAD implantation. Median time from listing to LVAD surgery was 21 (IQR 4-114) days. A total of 48% had poor FS at listing before LVAD. Patients with poor FS were younger, had lower body mass index (BMI), more likely to be on inotrope at listing and had worse hemodynamics. Time to LVAD implantation was shorter in poor FS group but no difference in LVAD support duration. There was no significant difference between poor FS and good FS group in 30-day (96.5% vs. 96.1%, p=0.59) and 1-year post-HTX survival (90.2% vs. 88.7%, p=0.23). Poor FS did not significantly affect 30-day (adjusted OR = 0.9, p=0.64) or 1-year post-HTX survival (adjust OR = 0.9, p=0.54). Of 1,342 patients with pre-LVAD poor FS, 715 (53%) had improvement in FS at HTX. Predictors of FS improvement were longer LVAD support duration and lower BMI. Among pre-LVAD poor FS group, patients with improved FS had significantly higher 1-year post-HTX survival (92.1% vs. 88.0%, p=0.015) but no significant difference in 30-day post-HTX survival (97.0 % vs. 95.8%, p=0.223). Improved FS in patients with pre-LVAD poor FS was significantly associated with higher 1-year survival (adjusted OR = 1.6, p= 0.03). Conclusions Poor functional status was observed in up to 50% of BTT-LVAD candidates; however, it doesn't negatively affect post-HTX survival. After BTT-LVAD support, half of patients with pre-LVAD poor FS have improved FS which is significantly associated with higher post-HTX survival. Urgent BTT-LVAD in selected patients with poor FS is a reasonable option prior to HTX.

Left Ventricular Assist Device Therapy and Acute Pancreatitis: Higher Incidence and Worse Clinical Outcomes.

The aim of the study was to compare incidence and outcomes of acute pancreatitis among advanced heart failure therapies. Two retrospective cohorts are as follows: A, patients with heart failure presenting to our hospitals and B, the US National Inpatient Sample. Three groups were compared: left ventricular assist device (LVAD) recipients, transplant recipients, and controls who did not qualify for advanced therapies. Primary outcomes were pancreatitis incidence and mortality. Secondary outcomes included kidney failure, multiorgan failure, shock, and health care utilization. Cohort A included 1344 heart failure patients, and cohort B included 677,905 patients with acute pancreatitis. In cohort A, annual pancreatitis incidence was 6.7 cases per 1000 LVAD recipients, 4.1 per 1000 LVAD bridge-to-transplant, 2.3 per 1000 transplant recipients, and 3.2 per 1000 heart failure controls (P = 0.03). Combined, the incidence was 5.6 per 1000 LVAD users and 2.7 in 1000 non-LVAD users (relative risk, 2.1; P = 0.009). In cohort B, increased mortality was seen in LVAD users, but not in transplant recipients. Left ventricular assist device patients had higher odds of kidney failure, multiorgan failure, shock, and intensive care. Patients with LVAD have double risk of pancreatitis, worse clinical outcomes, and increased healthcare utilization. Studies elucidating the mechanisms behind pancreatic injury in advanced heart failure are suggested.

Implication of Hemodynamic Assessment during Durable Left Ventricular Assist Device Support.

Durable left ventricular assist device therapy has improved survival in patients with advanced heart failure refractory to conventional medical therapy, although the readmission rates due to device-related comorbidities remain high. Left ventricular assist devices are designed to support a failing left ventricle through relief of congestion and improvement of cardiac output. However, many patients still have abnormal hemodynamics even though they may appear to be clinically stable. Furthermore, such abnormal hemodynamics are associated with an increased risk of future adverse events including recurrent heart failure, gastrointestinal bleeding, stroke, and pump thrombosis. Correction of residual hemodynamic derangements post-implantation may be a target in improving longitudinal clinical outcomes during left ventricular assist device support. Automatic and timely device speed adjustments considering a patients’ hemodynamic status (i.e., with a smart pump) are potential improvements in forthcoming devices.

Ventricular Assist Device Therapy for Patients with Severe Heart Failure

Ventricular Assist Device Therapy for Patients with Severe Heart Failure

Outcomes with Ventricular Assist Device Therapy for Advanced Heart Failure in North Macedonia: First Annual Report

Mechanical circulatory support by a continuous-flow ventricular assist device (VAD) improves survival and quality of life in selected patients with advanced heart failure. Developing countries have been struggling to construct a contemporary and effective health care system to manage advanced heart failure. This observation represents the first annual report on clinical outcomes with VAD for patients with advanced heart failure in the Republic of North Macedonia. Data from all patients with VAD implantations between November 2018 and December 2019 were collected. The etiology of the heart failure was dilated cardiomyopathy in 4 patients (57%), ischemic cardiomyopathy in 2 (28%), and hypertrophic cardiomyopathy in 1 (14%). The primary outcome was survival; secondary outcomes included adverse events defined according to the Interagency Registry for Mechanically Assisted Circulatory Support. A total of 7 patients (85% males, median age 56 years) received a VAD; 5 of them received left VAD, and the remaining 2 received biventricular VAD. There were no deaths. Observed morbidity during a mean follow-up of 216 days included 3 bleeding events in 1 patient, 2 patients with superficial driveline infection, and 1 minor stroke and a pump thrombosis, which were treated with VAD exchange. Significant improvement in quality of life, as assessed by the Kansas City Cardiomyopathy Questionnaire and the Functional Independence Measure™ instrument, was seen with all patients. Our results demonstrate a successful initiation of the VAD program in the Republic of North Macedonia. Proper training of a dedicated HF team supports the reproducibility of this treatment in developing countries.

Short- and long-term outcomes of continuous-flow left ventricular assist device therapy in 79 patients with end-stage heart failure.

An increasing number of patients with end‑stage heart failure, along with a shortage of heart donors, necessitates the use of mechanical circulatory support. This single‑center retrospective study evaluated short- and long term outcomes of continuous‑flow left ventricular assist device (CF LVAD) therapy in patients with end stage heart failure. We collected and assessed data of 79 patients (77 men, 2 women; mean age, 50.3 years; mean INTERMACS profile, 3.1) implanted with a CF‑LVAD between 2009 and 2017 (HeartMate 3 in 19 patients [24%]; HeartMate 2 in 9 [11.4%]; and HeartWare in 51 [64.6%]). The mean time on CF-LVAD support was 604 days (range, 1–1758 days). There were 2 device exchanges due to pump thrombosis and 1 explantation due to heart regeneration; 9 patients (11.4%) underwent heart transplant. Stroke (nondisabling, 48%) occurred in 27.8% of patients (ischemic in 9 patients; hemorrhagic, in 14; both types, in 1) despite the standardized anticoagulation regimen. Major gastrointestinal bleeding and pump thrombosis were reported in 13 patients (16.5%), while 18 patients (22.8%) developed driveline infections (recurrent in 15 patients [19%]). Hemorrhagic stroke and bacteremia had a negative impact on survival. Hemorrhagic stroke was the main cause of death. Survival probability was 0.9 at 1 month and 0.81, 0.71, 0.61, and 0.53 at 1, 2, 3, and 4 years, respectively. Although CF‑LVAD support is associated with substantial adverse events, they do not significantly affect mortality (except hemorrhagic stroke and bacteremia). Novel devices seem to overcome these limitations, but larger studies are needed to support these findings.

Current results of left ventricular assist device therapy in France: the ASSIST-ICD registry.

Our goal was to provide a picture of left ventricular assist device (LVAD) activity in France between 2007 and 2016 based on the multicentric ASSIST-ICD registry. We retrospectively collected 136 variables including in-hospital data, follow-up survival rates and adverse events from 671 LVAD recipients at 20 out of 24 LVAD implant centres in France. The average follow-up time was 1.2 years (standard deviation: 1.4); the total follow-up time was 807.5 patient-years. The included devices were the HeartMate II®, HeartWare LVAS® or Jarvik 2000®. The overall likelihood of being alive while on LVAD support or having a transplant (primary end point) at 1, 2, 3 and 5 years postimplantation was 65.2%, 59.7%, 55.9% and 47.7%, respectively, given a cumulative incidence of 29.2% of receiving a transplant at year 5. At implantation, 21.5% of patients were on extracorporeal life support. The overall rate of cardiogenic shock at implantation was 53%. The major complications were driveline infection (26.1%), pump pocket or cannula infection (12.6%), LVAD thrombosis (12.2%), ischaemic (12.8%) or haemorrhagic stroke (5.4%; all strokes 18.2%), non-cerebral haemorrhage (9.1%) and LVAD exchange (5.2%). The primary end point (survival) was stratified by age at surgery and by the type of device used, with inference from baseline profiles. The primary end point combined with an absence of complications (secondary end point) was also stratified by device type. The ASSIST-ICD registry provides a real-life picture of LVAD use in 20 of the 24 implant centres in France. Despite older average age and a higher proportion of patients chosen for destination therapy, survival rates improved compared to those in previous national registry results. This LVAD registry contrasts with other international registries because patients with implants have more severe disease, and the national policy for graft attribution is distinct. We recommend referring patients for LVAD earlier and suggest a discussion of the optimal timing of a transplant for bridged patients (more dismal results after the second year of support?).

Significant Restrictive or Obstructive Lung Diseases are Associated with an Increased Risk of Gastrointestinal Bleeding in Patients on Left Ventricular Assist Device Support

Despite the recent advances in Left Ventricular Assist Device (LVAD) therapy, gastrointestinal bleeding (GIB) remains a frequent and severe complication. A growing body of evidence suggests that the combination of hypoperfusion and hypoxia in the microcirculation may activate the angiogenesis cascade and promote the formation of arteriovenous malformations. We hypothesized that LVAD patients with concomitant significant restrictive or obstructive lung diseases may have an increased risk of GIB due to their chronic hypoxemic state. We retrospectively identified 99 patients on HeartMate II LVAD support (age 54±13 y, 77% male, 36% ischemic etiology) who had a pulmonary function test (PFT) performed. Significant lung disease was defined as a moderate or severe obstructive/restrictive pattern detected during PFT and the concomitant use of inhaler therapy. GIB was defined as clinical evidence of GI bleeding and a decrease in hemoglobin of at least 1 g/dL. 11 patients (11%) had significant lung disease and 27 patients (27%) experienced a GIB. The risk of GIB was increased in patients with significant lung diseases (Hazard Ratio 2.59, 95% confidence interval 1.038 to 6.452). Freedom from GIB was significantly higher in patients without significant lung disease in Kaplan-Meier analysis (Figure). Significant obstructive or restrictive lung diseases were associated with an increase in the risk of GIB. Further studies on the association of tissue hypoxia and activation of the angiogenesis cascade/bleeding diathesis in LVAD patients are warranted.

Haemodynamic Response of Pulmonary Hypertension Secondary to Left Heart Disease with Continuous Flow Left Ventricular Assist Device Therapy (CF-LVADS): Post-Transplant Outcomes

LVAD implantation is often utilised as a bridge to transplantation or candidacy in those with pulmonary hypertension secondary to left heart disease (PHLHD). Pulmonary hypertension portends poorer outcomes post-transplant. We compared pre and post implantation haemodynamic response and outcomes in patients who normalise transpulmonary gradient (TPG) to those who do not. Retrospective review of CF-LVAD patients was conducted for right heart catheter derived haemodynamic measurements and post-transplant outcomes from a single instituition. 219 CF-LVADs were implanted between October 2004 and September 2019. 48 patients had TPG greater than 12 prior to implantation. 1 patient was excluded for incomplete data. 28 patients normalised TPG (Gp 1) and 17 patients had elevated TPG (Gp 2) at first follow up. Table 1 describes the haemodynamic assessment of the two groups. At baseline, Gp 1 patient had significantly lower PVR, p=0.04. At follow-up, Gp 1 patients had significantly lower RAP, p<0.0001 and PP, =0.003. Gp 1 patients were more likely to survive on pump, p=0.03, more likely to be transplanted, p=0.03 and survived longer post transplant, p=0.04. Baseline pulmonary vascular resistance may provide prognostic information in CF-LVAD patients with PHLHD. Early normalization in TPG is associated with favourable haemodynamic response.

Efficacy of Left Ventricular Assist Device Therapy in Cold and Dry Chronic Heart Failure Patients

LVAD therapy has been primarily studied in patients with elevated pulmonary capillary wedge pressure (PCW) and low cardiac index (CI), "cold and wet". In daily practice, LVADs are often also offered to patients with low PCW and low CI, "cold and dry". The efficacy of LVAD therapy in this population is not well studied. Patients implanted with LVAD with a baseline CI <2.0 Lpm were categorized as "wet" (PCW>18mmHg) or "dry" (PCW<18mmHg). These values were derived from serial pre-LVAD right heart catheterization studies in order to reflect a sustainable hemodynamic profile. Variables of interest and 3-year survival were compared between groups. Independent predictors of mortality were identified using multivariate Cox regression analysis. Serial invasive hemodynamics data was available for 92 pts (cold-dry group, n=34 and cold-wet group, n=58) (Table). Diuretic and vasodilator use pre-LVAD was comparable in both groups. Cold-dry patients had no change in CVP or PCW with a smaller increase in CI after LVAD. Adjusted 3-year mortality was higher for cold-dry patients (Figure). Age (HR=1.09, 95%CI 1.02-1.2; p=006) and cold-dry profile (HR=5.4, 95%CI 1.4-21; p=0.016) were identified as independent predictors of mortality. "Cold and dry" patients with advanced heart failure may not derive equal benefit from LVAD therapy as those who are "cold and wet". This observation warrants further investigation.

Correction of High Afterload Improves Low Cardiac Output in Patients Supported on Left Ventricular Assist Device Therapy.

There is a paucity of data describing the invasive assessment of afterload and influence on cardiac output in patients supported on left ventricular assist device (LVAD) therapy. From 2015 to 2018, patients on LVAD therapy were evaluated with simultaneous left/right heart catheterization ramp study for speed optimization. Hemodynamic parameters from 31 patients without significant aortic insufficiency were analyzed. Mean central aortic pressure (MAP) was elevated at 87 ± 13 mm Hg at baseline. No direct association between MAP and cardiac index (CI) was found (r = 0.11, p = 0.20). However, variable MAP provided vastly different patterns of cardiac output response to speed increments (positive correlation, p = 0.047 for MAP <80 mm Hg; negative trend, p = 0.25 for MAP > 100 mm Hg). Patients noted to be hypertensive (MAP > 90, n = 8) received nitrate therapy and experienced both improvement in biventricular filling pressures and a mean increase in CI from 2.4 to 2.9 L/min/m2 (+22%, p = 0.04) at a fixed revolutions per minute. High afterload is common in patients on LVAD therapy, is associated with poor response to ramp, and is ameliorated by nitrates. These findings serve as a foundation to evaluate the dynamic effects of high afterload and chronic vasodilator therapy in patients with durable LVADs.

VAD 911: Process Improvement for First Responders Treating Ventricular Assist Device Patients.

Ventricular assist devices (VAD) complications including stroke, device failure, gastrointestinal bleeding, and infection all can manifest in the outpatient environment. Often, first responders do not have the knowledge base to respond appropriately. This study conducted an assessment of first responders generalized knowledge and self-reported competency regarding VAD use, provided an education course, and tested for improvement immediately after and 1 month postintervention. Two hundred thirty-six first responders participated from communities with known VAD patients. Responses indicated poor knowledge, experience, and competency. Twenty-one percent had seen a manufacturer training video, 26% had attended prior training, and 38% knew who to contact with a VAD emergency. Generalized knowledge of VAD therapy was poor with majority not understanding use of anticoagulation, when to initiate chest compressions and assessment variations. Self-reported competency was low with 80% of participants reporting unsafe to marginal about VAD awareness. Comparison of 1 month postintervention to preintervention, generalized knowledge improved by a minimum of 38% for each question and competency increased by over 50%. From this study comes the recommendation that VAD centers must include the community first responders as part of their discharge planning for the VAD patient and improve community outreach to ensure appropriate patient outcomes.

Comparing short‐term outcome after implantation of the HeartWare® HVAD® and the Abbott® HeartMate 3®

AimsCentrifugal continuous flow pumps are currently the state of the art in left ventricular assist device therapy. This study was conducted to compare the results after implantation of the HVAD® and the HeartMate 3®.Methods and resultsWe retrospectively analysed preoperative and post‐operative patient data of all 106 patients, who received a HeartMate 3 (HM3) at our centre between 2014 and 2018. A total of 392 patients receiving a sintered HVAD® served as controls. Patient matching was performed for age, sex, Interagency Registry for Mechanically Assisted Circulatory Support level at the time of implant, perioperative right heart failure, and implantation strategy, that is, bridge to transplant or destination therapy, as well as preoperative renal function, that is, as indicated by serum creatinine levels. A total of 79 matched pairs could be identified. During a median follow‐up of 15.3 months (range: 0–30 months), 23 (29.1%) and 19 (24.1%) patients died in the HVAD and HM3 groups, respectively, with a hazard ratio for mortality of 0.84 [95% confidence interval (CI): 0.46–1.54; P = 0.568]. Freedom from cerebrovascular events did not differ significantly between study groups, with a hazard ratio of 0.57 (95% CI: 0.23–1.45; P = 0.241). The risk of driveline infection was significantly lower in the HM3 (n = 33) than in the HVAD (n = 55) group (hazard ratio = 0.54; 95% CI: 0.35–0.84; P = 0.006). Eight HVAD, but no HM3, patients developed a pump thrombosis during follow‐up (P = 0.148).ConclusionsPerformance of both currently used centrifugal left ventricular assist device systems is comparable in terms of short‐term patient survival and freedom from cerebrovascular events. In our single‐centre experience, HM3 patients less frequently develop driveline infections and no pump thrombosis, which requires further evaluation.

Population Pharmacokinetics of Vancomycin in the Pediatric Ventricular Assist Device Population

Determine the pharmacokinetic disposition of vancomycin in the pediatric ventricular assist device population. A retrospective, population pharmacokinetic study. Large, quaternary care children's hospital. Less than 19 years old initiated on vancomycin while undergoing ventricular assist device therapy from 2011 to 2018 in our institution. Patient data were summarized by using descriptive statistical methods, and population pharmacokinetic analysis was performed by using NONMEM (Icon, PLC, Dublin, Ireland). Simulation was performed to identify a vancomycin dosing strategy that resulted in a trough concentration less than 15 mg/L and an area under the curve0-24:minimum inhibitory concentration ratio of greater than 400. A total of 69 patients (male 50.7%, median age 7.1 years [interquartile range, 2.4-11.9]) met study criteria (HeartWare [Framingham, MA] = 37, Berlin Heart [Berlin, Germany] = 22, Impella [Abiomed, Danvers, MA] = 4, RotaFlow [Maquet, Hirrlingen, Germany] right ventricular assist device = 3, HeartMate II [Abbott Laboratories, Abbott Park, IL] = 2, Berlin Heart biventricular assist device = 1). Patients received a median of 21 doses (interquartile range, 13-44 doses) of IV vancomycin (14.8 ± 1.8 mg/kg/dose) along with vancomycin as an intrathoracic irrigation (n = 48; 69.6%). The mean serum concentration was 12.2 ± 5.2 mg/L at 11.2 ± 6.9 hours after a dose. A one-compartment pharmacokinetic model best fit the data with allometric scaling on clearance and volume of distribution. Clearance was characterized by total body weight and serum creatinine, and volume of distribution was characterized by total body weight. Simulation identified doses greater than 15 mg/kg/dose with extended intervals were necessary to achieve endpoints. Vancomycin dosing in pediatric ventricular assist device patients should be altered in comparison to nonventricular assist device patients and should be accompanied with frequent serum concentration monitoring.

A right ventricular state of mind in the progression of heart failure with reduced ejection fraction: implications for left ventricular assist device therapy.

Right ventricular (RV) function in patients with preexisting left ventricular (LV) systolic dysfunction is key to determining prognosis and identifying appropriate candidates for cardiac replacement therapy. This becomes particularly relevant during selection for left ventricular assist device (LVAD) therapy, since adequate cardiac output, differently from heart transplantation, still relies on native RV function. Importantly, accumulating evidence indicates that RV failure (RVF) carries detrimental consequences of progressive end-organ dysfunction due to systemic venous congestion-mediated inflammation and oxidative stress. Therefore, it is crucial to detect RVF early on in the disease state through heightened clinical suspicion and noninvasive and/or invasive modalities before the RV fails and organ damage ensues, precluding patients from life saving measures such as LVAD therapy. The purpose of this review is to discuss the pathogenesis of RVF, its systemic consequences, implications for pre- and post-LVAD management, and its impact on clinical outcomes.